The Renewed National Cervical Screening Program 2019 Common Questions and Cases Preventing cervical cancer Australia - National HPV vaccination program - The National cervical screening program Annabelle Farnsworth Director Cervical Screening, Douglass Hanly Moir Pathology Professor of Pathology; University of Notre Dame, Sydney School of Medicine The New National Cervical Screening Program 1 st December 2017 - Primary HPV testing with partial genotyping and cytology triage - Commencing at age 25 years - Every 5 years - Exit HPV test 70-74 years, can continue on Medicare - Self testing for under-screened women Management guidelines - 2016 Guidelines http://wiki.cancer.org.au/australia/guidelines:cervical_cancer/screening - 2016 Guidelines online education - scenarios http://wiki.cancer.org.au/australia/guidelines:cervical_cancer/screening/e-learning
Population screening Complex Public Health program Issues relevant at a time of great change Population screening Complex Public Health program Issues relevant at time of great change - Ethical issues in population screening: balance of benefits and harms - "The ethical imperative with all medical interventions is to endeavour to ensure that potential benefits will outweigh harm. This is particularly so of screening. If a patient asks a doctor for help the doctor is obliged to do his or her best to help but (if) the doctor initiates a screening program there is a presumption that this must benefit the patient - A program should, at the very least, be able to demonstrate evidence of an overall benefit to the community - And a minimum of risk that certain individuals may be disadvantaged by the program - Not only is it important that information on the effectiveness of screening programs be available, it should also be disseminated widely https://wiki.cancer.org.au/policy/principles_of_screening#ethical_issues_in_population_screening:_balance_of_benefits_and_har ms https://wiki.cancer.org.au/policy/principles_of_screening#ethical_issues_in_population_screening:_balance_of_benefits_and_harms Issues that have arisen in first year - Self collection SCREENING VS. NON SCREENING - National Cancer Screening Register (NCSR) - HPV testing in practice - screening versus non-screening - older women - HPV testing - a little more detail Women over 25 years, main screening pathway Self collection Symptoms, follow up Sample as for main pathway but may have HPV co-test done at same time Why self collection? - Major issue with screening programs RECRUITMENT 68 66 64 PARTICIPATION IN CERVICAL SCREENING PERCENTAGE OF ELIGIBLE WOMEN BY STATE 2000-2001 2015-2016 Australia 2000-2001 Australia 2015-2016 - Acknowledged as part of major review undertaken 62 60 58 - Participation has fallen by 50% in the last 10 years 56 54 52 50 NSW Vic Qld WA SA Tas ACT NT Sources: Data taken from AIHW Cervical screening publications: - Cervical screening 2015-2016 - Cervical screening in Australia 2000-2001 and 1999-2000
Self collection Self collection option - Recognised solution for women who won t screen - Aged 30-74 years - Possible now there are reliable HPV tests - NOT for cytology e.g. Solopap - Women who have not screened for 2 years longer than recommended interval - 4 years in the first round - 7 years future MEDICARE RESTRICTED!! Self collect SELF COLLECTING DEVICE RED TOP FLOQ SWAB - Screening samples only - Directed by Primary Care Giver - To be done in clinic - Not to be taken home - NOT posted Self collected HPV tests - The availability of self collection in the screening program has been limited - Each individual testing laboratory must validate the collection method - VCS only laboratory with accreditation for most of 2018
Self collect validation study Self collect data - Individual lab validation requires a study protocol and ethics approval with the collection of dual samples (self collect plus Dr collect) from 200-300 women - DHM and FPNSW undertook study, March June2018-223 women - Excellent correlation - Approved by NATA, TGA and testing is now being performed at DHM in Sydney SELF COLLECT (vaginal) TOTAL hrhpv- HrHPV+ CLINICIAN COLLECT (cervical) HrHPV+ hrhpv- TOTAL 30 5 35 0 188 188 30 193 223 Sensitivity = 100%; Specificity = 97% Concordance = 98%; Kappa = 0.910 (95%CI 0.833-0.988) Source: Validation of Patient-Collected Vaginal Swabs for Use in the Roche cobas 6800 HPV Assay Ms AJ 35 year old Ms AJ 35 year old - Known patient usually comes with her children - Presents with infected finger - Classic paronychia - Note she hasn t ever had cervical screening - Ask about it - Flatly refuses - Suggest self sampling - Returns 2 weeks later - Provide her with FLOQ swab and directions - She takes sample in the bathroom - Send it off to the lab - Treat paronychia - Give her brochure re self sampling and ask her to return
Ms AJ 35 year old NCSR - Positive for other, non 16/18 - Needs to return to you for cytology sample - Happy to do - Visualize cervix, take LBC - Report: negative, recommend repeat 12 months time - NCSR will follow-up - Numerous delays - State data transfer completed Mid 2018 - But functionality has been poor - patient histories - recruitment - 25 year olds invitation letter - Follow-up OK NCSR - Clinical interface still planned for 2020 - Bowel screen to be included 2019 - Because of Medicare linkage have identified large numbers of unscreened women - Important role is provision of data to monitor program Co-testing SCREENING VS. NON SCREENING - HPV and LBC ordered at same time Women over 25 years, main screening pathway Self sampling Symptoms, follow up Sample as for main pathway but may have HPV co-test done at same time - Concerns re too much co-testing?!
Why co-test? Ms JS 46 year old - Why was co-testing included? - false negative HPV tests - data from US - co-testing recommended, not an organised screening program - approx. 6% negative HPV with known high grade abnormality - less than Pap smear - Clinical notes - last pap smear 10 years ago - history of post coital bleeding - abnormal uterine bleeding - polyp anterior lip - bulky uterus - SYMPTOMATIC - co-test for symptoms and signs requested by GP HPV DNA test - HPV 16 Not Detected - HPV 18 Not Detected - HR HPV (not 16/18) Not Detected CST This whole field is exophytic tumour, 3cm at least - Risk Category * HIGHER RISK - TEST RESULTS PCR for Oncogenic HPV and Genotype - HPV16 Not Detected - HPV18 Not Detected - HPV(not 16/18) Not Detected - Cytology Category * Squamous Cell Carcinoma - Specific Findings Endocervical component is present - Recommendation Refer for colposcopic assessment
- Patient has a clinical stage 2B, 4-5cm tumour on palpation with left parametrial involvement - Chemotherapy and radiotherapy only at this stage - Routine cervical screening using primary human papillomavirus (HPV) testing: Early observations from the renewed National Cervical Screening Program Dorothy A Machalek, Jennifer M Roberts, Suzanne M Garland, Julia Thurloe, Adele Richards, Ian Chambers, Terri Sivertsen, Annabelle Farnsworth - Data from DHM Sydney, Australia - First 6 months - Submitted for publication Reasons for referral among 195,606 samples received for HPV testing, and overall HPV positivity among valid tests Summary Reason for HPV test Sample received β-globin positive (valid) tests Any Oncogenic HPV HPV16/18 Other oncogenic HPV only (not 16/18) - Primary screening, overall HPV positive rate 8.1% n (%) n (%) n % n % n % Primary screening 157,700 (80.6) 157,542 (99.9) 12,699 8.1 3,453 2.2 9,246 5.9 Non-screening 37,906 (19.4) 37,843 (99.8) 7,900 20.9 1,606 4.2 6,294 16.6 Follow-up for previous LSIL 6,118 (16.1) 6,096 (99.6) 2,106 34.6 380 6.2 1,726 28.3 - Non screening overall HPV positive rate 20.9% - symptoms or signs 15.4% - not classified 22.8% Co-test for previous AIS 49 (0.1) 49 (100.0) 4 8.2 1 2.0 3 6.1 Co-test for previous HSIL 9,682 (25.5) 9,672 (99.9) 1,708 17.7 532 5.5 1,176 12.2 Co-test for symptoms/signs 12,703 (33.5) 12,685 (99.9) 1,954 15.4 324 2.6 1,630 12.9 Co-test for other, indication 9,354 (24.7) 9,341 (99.8) 2,128 22.8 369 4.0 1,759 18.8 unknown Machalek et al. Routine cervical screening using primary HPV: early observations from the renewed cervical screening program. Co test for symptoms or signs of cervical disease (cancer) Ms CF 26 year old - Abnormal bleeding - post coital bleeding, intermenstrual, post menopausal - Dyspareunia - Discharge, unusual, red - Abnormal cervix - suspicious, friable, hard, irregular - Presents post coital bleeding - Due for cervical screening test - Take sample, order co-test (HPV and LBC) - request form post coital bleeding - Use opportunity for gynaecological check. - Also order chlamydia/gonorrhoea
Ms CF 26 year old Ms CF 26 year old - Laboratory: books patient in as Symptomatic - RESULT: - Risk category SYMPTOMATIC - oncogenic HPV Result positive not 16/18 - cytology negative BUT - Chlamydia test positive - Cause of bleeding - Treat - Recommendation repeat 12 months - appropriate investigation of noted symptoms and/or signs is advised Ms CF 26 year old False positive HPV tests - Even though HPV positive still classed as symptomatic, with Intermediate Risk report - Investigation of symptoms & signs DOESN T MEAN referral to GYNAECOLOGIST NECESSARILY - Over detection? - HPV testing increased sensitivity, decreased specificity - Can be managed by you! - Cervical screening no longer Pap smear - Has been seeing you regularly for years - Has received a letter from National Cancer Screening Register (NCSR) saying she is due for cervical screening test? - Has screened regularly with no abnormalities over last 20 years - HPV test - LBC cytology sample - Explain if negative won t need a test for five years
- Test result returns - HIGH RISK - HPV 16 Positive - cytology negative - Recommend colposcopy - Age-specific oncogenic HPV prevalence among 156,683 valid primary screening tests, women 25-74 Machalek et al. Routine cervical screening using primary HPV: early observations from the renewed cervical screening program. - Age-specific risk classification and management recommendations from 156,683 valid primary screening tests, women 25-74 - What does this mean? - recently acquired infection? - latent infection? - has had for years and is non-active virus - why colposcopy? Machalek et al. Routine cervical screening using primary HPV: early observations from the renewed cervical screening program. Absolute risks of CIN3 or worse after infection with different high-risk human papillomavirus (HPV) types in women with normal cytological findings at baseline. COLPOSCOPY - Atrophic cervix - Type 3 transformation zone - squamocolumnar junction not visible - No abnormality seen - Returns to you for advice on what she should do Source: Kjar JNCI 2010
Source: 2016 Guidelines http://wiki.cancer.org.au/australia/guidelines:cervical_cancer/screening Source: 2016 Guidelines http://wiki.cancer.org.au/australia/guidelines:cervical_cancer/screening Offering the best HPV test - Topical oestrogen before colposcopy - Have a ready explanation - Quality parameters - Quality control, quality assurance - HPV most likely present for years, not a recent infection - Management will be after discussion with individual patient - Research will be needed, good example of where colposcopy registry data may help Ms HB 27 year old Ms HB 27 year old - Routine screen - But history of irregular, intermenstrual bleeding - Ask for co-test - At time of sample notice some blood at os and contact bleeding - REPORT: - Unsatisfactory - HPV 16, 18, non 16/18 - invalid - Cytology - Negative - Repeat 6 weeks
Invalid HPV testing inhibited Invalid HPV testing sample adequacy control - Why invalid? - HPV testing - Internal Cellular control present for each sample - To detect where NO material is present - test can be inhibited by blood and other substances e.g. lubricant - the molecular reaction doesn t actually work - can be just one, just two or all three - Crucial in a screening program - no report can be issued New era of cervical screening - Self Collect testing now available at Douglass Hanly Moir - Routine patient management relatively straight forward - But occasional more complicated patient first do no harm Thank you Acknowledgments: Dorothy Machalek, Jennifer Roberts, Sue Garland, Ian Chambers, Julia Thurloe, Terri Sivertson Adele Richards - Be mindful of issues associated with screening programs: false negatives, false positives - Patients must be kept informed - Importance of monitoring Reasons for referral among 195,606 samples received for HPV testing, and overall HPV positivity among valid tests ) Reason for HPV test Sample received β-globin positive (valid) tests Any Oncogenic HPV HPV16/18 Other oncogenic HPV only (not 16/18) n (%) n (%) n % (95% CI) n % (95% CI) n % (95% CI) Primary screening 157,700 (80.6) 157,542 (99.9) 12,699 8.1 (7.9 8.2) 3,453 2.2 (2.1 2.3) 9,246 5.9 (5.8 6.0) Non-screening 37,906 (19.4) 37,843 (99.8) 7,900 20.9 (20.5 21.3) 1,606 4.2 (4.0 4.5) 6,294 16.6 (16.3 17.0) Follow-up for previous LSIL 6,118 (16.1) 6,096 (99.6) 2,106 34.6 (33.4 35.8) 380 6.2 (5.7 6.9) 1,726 28.3 (27.2 29.5) Co-test for previous AIS 49 (0.1) 49 (100.0) 4 8.2 (3.1 19.8) 1 2.0 (0.3 13.1) 3 6.1 (2.0 17.3) Co-test for previous HSIL 9,682 (25.5) 9,672 (99.9) 1,708 17.7 (16.9 18.4) 532 5.5 (5.1 6.0) 1,176 12.2 (11.5 12.8) Co-test for symptoms/signs 12,703 (33.5) 12,685 (99.9) 1,954 15.4 (14.8 16.0) 324 2.6 (2.3 2.8) 1,630 12.9 (12.3 13.4) Co-test for other, indication unknown 9,354 (24.7) 9,341 (99.8) 2,128 22.8 (21.9 23.6) 369 4.0 (3.6 4.4) 1,759 18.8 (18.1 19.6) Machalek et al. Routine cervical screening using primary HPV resulting in early observations from the renewed cervical screening program.